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1.
Front Cell Dev Biol ; 9: 737003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650984

RESUMO

Clinical demographics have demonstrated that postmenopausal women are predisposed to chronic stress-induced cardiomyopathy (CSC) and this has been associated with the decrease of estrogen. Meanwhile, recent studies have implicated unsolved myocardial proinflammatory responses, which are characterized by enormous CD86+ macrophage infiltrations as an underlying disease mechanism expediting the pathological remodeling of the heart during chronic stress. However, we had previously demonstrated that estrogen confers cardioprotection via the modulation of cardiomyocytes ß2-adrenoceptors (ß2AR)-Gs/Gi pathways during stress to lessen the incidence of stress-induced cardiovascular diseases in premenopausal women. Intriguingly, macrophages express ß2AR profoundly as well; as such, we sought to elucidate the possibilities of estrogen modulating ß2AR-Gs/Gi pathway to confer cardioprotection during stress via immunomodulation. To do this, ovariectomy (OVX) and sham operations (Sham) were performed on female Sprague-Dawley (SD) rats. Two weeks after OVX, the rats were injected with 40 µg/kg/day of estradiol (E2). Next, on day 36 after OVX, chronic stress was induced by a daily subcutaneous injection of 5 mg/kg/day of isoproterenol (ISO). The effect of E2 on relevant clinical cardiac function indexes (LVSP, LVEDP, + dp/dt and -dp/dt), myocardial architecture (cardiomyocyte diameter and fibrosis), ß2AR alterations, and macrophage (CD86+ and CD206+) infiltrations were assessed. In vitro, peritoneal macrophages (PMΦ) were isolated from wild-type and ß2AR-knockout female mice. The PMΦ were treated with ISO, E2, and ß2AR blocker ICI 118,551 for 24 h, and flow cytometric evaluations were done to assess their phenotypic expression. E2 deficiency permitted the induction of CSC, which was characterized by cardiac dysfunctions, maladaptive myocardial hypertrophy, unresolved proinflammatory responses, and fibrosis. Nonetheless, E2 presence/supplementation during stress averted all the aforementioned adverse effects of chronic stress while preventing excessive depletion of ß2AR. Also, we demonstrated that E2 facilitates timely resolution of myocardial proinflammation to permit reparative functions by enhancing the polarization of CD86+ to CD206+ macrophages. However, this adaptive immunomodulation is hampered when ß2AR is inhibited. Taken together, the outcomes of this study show that E2 confers cardioprotection to prevent CSC via adaptive immunomodulation of macrophage phenotypes, and ß2AR-mediated signaling is crucial for the polarizations of CD86+ to CD206+ macrophages.

2.
Technol Cancer Res Treat ; 20: 15330338211043975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34632869

RESUMO

Objective: To investigate the features of helical tomotherapy and co-planar dual Arcs volumetric-modulated arc therapy during prophylactic cranial irradiation associated with bilateral hippocampal tissue sparing. Materials and methods: Helical tomotherapy and co-planar dual arcs volumetric-modulated arc therapy treatment plans were generated with a dose of 30 Gy/10 fractions in 16 patients treated with prophylactic cranial irradiation. The dose to the bilateral hippocampal tissues, organs at risk, and planning target volume were determined when the average dose of bilateral hippocampal tissues was reduced by approximately 4 Gy as an observation point. Changes in dosimetry when sparing the bilateral hippocampal tissues were determined for both modalities. Results: When bilateral hippocampal tissues were restricted to 8 Gy, D40%mean-bilateral hippocampal tissues = 7.64 ± 0.41 Gy in helical tomotherapy, while D40%mean-bilateral hippocampal tissues = 10.96 ± 0.38 Gy in co-planar dual arcs volumetric-modulated arc therapy volumetric-modulated arc therapy. Helical tomotherapy was associated with significantly lower doses to organs at risk, including Dmean-bilateral hippocampal tissues (P = .03), D98%-bilateral hippocampal tissues (P = .01), D2%-bilateral hippocampal tissues (P = .01), Dmean-inner ear (P = .02), Dmean-parotid glands (P = .02), Dmax-lens (P = .02), and Dmax-brainstem (P = .02), but not Dmax-optic nerves (P = .87). Helical tomotherapy provided better target coverage, with lower average D2%-PTV (P = .02), higher average D98%-PTV (P = .02), and better conformal index (0.87 vs 0.84, P = .02) and homogeneity index (0.15 vs 0.21, P = .05). With smaller bilateral hippocampal tissues doses, the planning target volume dose changed across 3 dosimetry regions for both modalities; the plateau region (>20.0 Gy for helical tomotherapy versus >16.0 Gy for co-planar dual arcs volumetric-modulated arc therapy), gradient region (20.0-12.0 Gy vs 16.0-11.0 Gy), and falling region (<12.0 Gy vs <11.0 Gy). The average delivery duration of helical tomotherapy was almost 7.7 times longer than that of co-planar dual arcs volumetric-modulated arc therapy. Conclusions: Helical tomotherapy was better at sparing the bilateral hippocampal tissues and organs at risk and had better target coverage but a significantly longer treatment duration than co-planar dual arcs volumetric-modulated arc therapy. Further dose decreases in the bilateral hippocampal tissues would yield worse target dose coverage.

3.
J Asian Nat Prod Res ; : 1-9, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647509

RESUMO

Three new caffeoyl derivatives (1-3), together with two known ones (4-5), were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 4 was obtained and its NMR data were given for the first time. All isolates were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and pro-inflammatory cytokines release in RAW 264.7 cells. Compounds 2-5 showed mild inhibitory activities with IC50 values ranging from 64.78 to 87.21 µM, and 3-4 could inhibit LPS-induced tumor necrosis factor-α (TNF-α) production.

4.
BMC Med Educ ; 21(1): 484, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503514

RESUMO

BACKGROUND: The outbreak of COVID-19 has led to increased workload and infection risks among medical staff. This situation may influence current medical and health-related students' decision on the choices of their future careers. Hence, this study investigated the impact of COVID-19 on their future career intentions. METHODS: This is a cross-sectional observational study that included medical and health-related students from three universities between October 2020 and January 2021. The study questionnaire was divided into two main sections: Section 1, which comprised students' basic information. And section 2 focused mainly on the impact of COVID-19 pandemic on students' professional intentions. The chi-squared χ2 test was used to compare the responses before and after the pandemic outbreak among Chinese and non-Chinese students. RESULTS: In overall, 1253 students completed the questionnaires. The responses showed that the number of students who preferred clinical medicine, public health, pharmacy and oral medicine increased significantly after the pandemic outbreak. In contrast, the number of students who chose nursing and medical technology decreased significantly. The change mainly occurred in Chinese students, predominantly females. Half of students (50.35%) were more willing to engage in medical and health work after completing their current program. Also, 36.39% of students felt that knowledge was too limited in the pandemic's face and would like to continue studying after graduation to gain more knowledge. Due to the pandemic, 34.18% of students would like a future workplace near their hometown, and 19.63% preferred to work in urban areas. CONCLUSION: The COVID-19 outbreak impacted current medical and health-related students' career planning on their future workplaces and employment time choices. Additionally, the pandemic influenced the intention of Chinese students in choosing their future careers. This study provided the basis for the policymaking, specialty setting of colleges and supplied the medical health department's talent reserve information.


Assuntos
COVID-19 , Estudantes de Medicina , Estudos Transversais , Feminino , Humanos , Intenção , Masculino , Pandemias , SARS-CoV-2
5.
Front Pharmacol ; 12: 726015, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504430

RESUMO

Experimental and clinical evidence has indicated that the natural product ascorbic acid (AA) is effective in preventing and treating various types of cancers. However, the effect of AA on liver cancer metastasis has not yet been reported. Cancer stem cells (CSCs) play pivotal roles in cancer metastasis. Here, we demonstrated that AA selectively inhibited the viability of both liver cancer cells and CSCs, reduced the formation of cancer cell colonies and CSC spheres, and inhibited tumor growth in vivo. Additionally, AA prevented liver cancer metastasis in a xenotransplantation model without suppressing stemness gene expression in liver CSCs. Further study indicated that AA increased the concentration of H2O2 and induced apoptosis in liver CSCs. Catalase attenuated the inhibitory effects of AA on liver CSC viability. In conclusion, AA inhibited the viability of liver CSCs and the growth and metastasis of liver cancer cells in vitro and in vivo by increasing the production of H2O2 and inducing apoptosis. Our findings provide evidence that AA exerts its anti-liver cancer efficacy in vitro and in vivo, in a manner that is independent of stemness gene regulation.

7.
Cell Immunol ; 368: 104419, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34371260

RESUMO

Rheumatoid arthritis (RA) is a complicated rheumatic autoimmune disease. Lectin, galactoside-binding soluble, 2 (LGALS2), LGALS3 and LGALS9, three members of the galectin family, play potential roles in autoimmune diseases, including RA. However, association of genetic polymorphisms of LGALS2, LGALS3 and LGALS9 with RA risk in a Southern Chinese Han population has not been elucidated. A case-control study was conducted herein, including 500 RA patients and 650 healthy individuals of Southern Chinese Han origin. Twelve single nucleotide polymorphisms (SNPs), including rs7291467 for the LGALS2 gene, rs4644, rs4652, rs1009977, rs2274273 and rs17128183 for the LGALS3 gene, and rs4795835, rs3763959, rs4239242, rs3751093, rs732222 and rs4794976 for the LGALS9 gene, were genotyped. Polymorphisms were genotyped using the KASP method. Frequencies of rs1009977 genotype TG and rs3751093 genotype GA of LGALS3 gene were significantly different between RA patients and healthy controls (P = 0.049, P = 0.033). Allele T and genotypes TT and TT + TG of rs4794976 for LGALS9 gene were significantly correlated with RA risk (P = 0.017, P = 0.012, P = 0.041). Subgroup analysis revealed that rs1009977, rs2274273 and rs17128183 polymorphisms of LGALS3 gene and rs4795835 polymorphism of LGALS9 gene were correlated with several RA clinical manifestations (all P < 0.05). In addition, haplotype GCGTT showed an increased risk for RA (OR = 1.216, 95% CI: 1.028-1.438, P = 0.023), whereas haplotype GCGTG showed a reduced risk for RA susceptibility (OR = 0.779, 95% CI: 0.625-0.971, P = 0.026). In conclusion, LGALS3 and LGALS9 gene polymorphisms may associate with RA predisposition in a Southern Chinese Han population.

8.
Asian J Androl ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34213488

RESUMO

Peroxisome proliferator-activated receptors γ (PPARγ) is a master regulator that controls energy metabolism and cell fate. PPARγ2, a PPARγ isoform, is highly expressed in the normal prostate but expressed at lower levels in prostate cancer tissues. In the present study, PC3 and LNCaP cells were used to examine the benefits of restoring PPARγ2 activity. PPARγ2 was overexpressed in PC3 and LNCaP cells, and cell proliferation and migration were detected. Hematoxylin and eosin (H&E) staining was used to detect pathological changes. The genes regulated by PPARγ2 overexpression were detected by microarray analysis. The restoration of PPARγ2 in PC3 and LNCaP cells inhibited cell proliferation and migration. PC3-PPARγ2 tissue recombinants showed necrosis in cancerous regions and leukocyte infiltration in the surrounding stroma by H&E staining. We found higher mixed lineage kinase domain-like (MLKL) and lower microtubule-associated protein 1 light chain 3 (LC3) expression in cancer tissues compared to controls by immunohistochemistry (IHC) staining. Microarray analysis showed that PPARγ2 gain of function in PC3 cells resulted in the reprogramming of lipid- and energy metabolism-associated signaling pathways. These data indicate that PPARγ2 exerts a crucial tumor-suppressive effect by triggering necrosis and an inflammatory reaction in human prostate cancer.

9.
Int J Mol Sci ; 22(14)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34299294

RESUMO

Nitrogen (N) is an essential nutrient for plant growth and development. The root system architecture is a highly regulated morphological system, which is sensitive to the availability of nutrients, such as N. Phenotypic characterization of roots from LY9348 (a rice variety with high nitrogen use efficiency (NUE)) treated with 0.725 mM NH4NO3 (1/4N) was remarkable, especially primary root (PR) elongation, which was the highest. A comprehensive analysis was performed for transcriptome and proteome profiling of LY9348 roots between 1/4N and 2.9 mM NH4NO3 (1N) treatments. The results indicated 3908 differential expression genes (DEGs; 2569 upregulated and 1339 downregulated) and 411 differential abundance proteins (DAPs; 192 upregulated and 219 downregulated). Among all DAPs in the proteome, glutamine synthetase (GS2), a chloroplastic ammonium assimilation protein, was the most upregulated protein identified. The unexpected concentration of GS2 from the shoot to the root in the 1/4N treatment indicated that the presence of an alternative pathway of N assimilation regulated by GS2 in LY9348 corresponded to the low N signal, which was supported by GS enzyme activity and glutamine/glutamate (Gln/Glu) contents analysis. In addition, N transporters (NRT2.1, NRT2.2, NRT2.3, NRT2.4, NAR2.1, AMT1.3, AMT1.2, and putative AMT3.3) and N assimilators (NR2, GS1;1, GS1;2, GS1;3, NADH-GOGAT2, and AS2) were significantly induced during the long-term N-deficiency response at the transcription level (14 days). Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that phenylpropanoid biosynthesis and glutathione metabolism were significantly modulated by N deficiency. Notably, many transcription factors and plant hormones were found to participate in root morphological adaptation. In conclusion, our study provides valuable information to further understand the response of rice roots to N-deficiency stress.


Assuntos
Glutamato-Amônia Ligase/metabolismo , Nitrogênio/deficiência , Oryza/genética , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Glutamato-Amônia Ligase/genética , Nitrogênio/metabolismo , Oryza/enzimologia , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/genética , Proteínas de Plantas/genética , Raízes de Plantas/genética , Proteômica/métodos , Estresse Fisiológico/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
10.
Microb Pathog ; 158: 105053, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34147587

RESUMO

Human parainfluenza virus type 3 (hPIV-3) entry and intrahost spread through membrane fusion are initiated by two envelope glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F) protein. Binding of HN protein to the cellular receptor via its receptor-binding sites triggers conformational changes in the F protein leading to virus-cell fusion. However, little is known about the roles of individual amino acids that comprise the receptor-binding sites in the fusion process. Here, residues R192, D216, E409, R424, R502, Y530 and E549 located within the receptor-binding site Ⅰ, and residues N551 and H552 at the putative site Ⅱ were replaced by alanine with site-directed mutagenesis. All mutants except N551A displayed statistically lower hemadsorption activities ranging from 16.4% to 80.2% of the wild-type (wt) level. With standardization of the number of bound erythrocytes, similarly, other than N551A, all mutants showed reduced fusogenic activity at three successive stages: lipid mixing (hemifusion), content mixing (full fusion) and syncytium development. Kinetic measurements of the hemifusion process showed that the initial hemifusion extent for R192A, D216A, E409A, R424A, R502A, Y530A, E549A and H552A was decreased to 69.9%, 80.6%, 71.3%, 67.3%, 50.6%, 87.4%, 84.9% and 25.1%, respectively, relative to the wt, while the initial rate of hemifusion for the E409A, R424A, R502A and H552A mutants was reduced to 69.0%, 35.4%, 62.3%, 37.0%, respectively. In addition, four mutants with reduced initial hemifusion rates also showed decreased percentages of F protein cleavage from 43.4% to 56.3% of the wt. Taken together, Mutants R192A, D216A, E409A, R424A, R502A, Y530A, E549A and H552A may lead to damage on the fusion activity at initial stage of hemifusion, of which decreased extent and rate may be associated with impaired receptor binding activity resulting in the increased activation barrier of F protein and the cleavage of it, respectively.


Assuntos
Proteína HN , Vírus da Parainfluenza 3 Humana , Sítios de Ligação , Proteína HN/genética , Proteína HN/metabolismo , Humanos , Mutagênese Sítio-Dirigida , Vírus da Parainfluenza 3 Humana/genética , Ligação Proteica , Proteínas Virais de Fusão/genética , Internalização do Vírus
11.
Cardiovasc Res ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34155498

RESUMO

AIMS: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and absence of coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. METHODS AND RESULTS: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal) cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavß subunit), RGS4 (regulator of G-protein signalling 4) and G-protein subunit Gß (GNB1) as underlying these effects. CONCLUSION: miR-16 and miR-26a sensitise the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future. TRANSLATIONAL PERSPECTIVE: TTS-associated miRs have the potential to be active players predisposing to TTS. Feasibly, their measurement in recovered TTS patients during subsequent periods of stress could be used to predict likelihood of recurrence, a significant risk in this population, and allow preventative action. Since they have been reported as raised in anxiety and depression, they could be part of a priming mechanism where chronic stress predisposes to an acute episode. Understanding the mechanistic basis for the sensitisation may also allow design of other prophylactic pharmacological therapies, including the pre/anti-miR constructs which are now starting to reach the clinic.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33936245

RESUMO

Objective: To perform a systematic evaluation of the efficacy and safety of combined treatment of Shenmai injection and chemotherapy for lung cancer. Methods: A literature search for randomized controlled trials (RCTs) describing the treatment of lung cancer by Shenmai injection and chemotherapy or chemotherapy alone was performed using the PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Value In Paper (VIP), China BioMed, and Wanfang databases. The databases were searched for entries published before September 1, 2019. Results: Thirty-seven RCTs, comprising a total of 2808 cases, were included in the present meta-analysis. Of these, 1428 cases were treated by Shenmai injection plus chemotherapy, and 1380 cases were treated only by chemotherapy. The results of meta-analysis showed that the combined treatment (Shenmai injection plus chemotherapy) increased the short-term efficacy of treatment (relative risk [RR] = 1.183, 95% confidence interval [CI] = 1.043-1.343, P < 0.01) and improved patients' quality of life (RR = 1.514, 95%CI = 1.211-1.891, P < 0.01) compared with chemotherapy alone. With regard to the adverse effects, the combined treatment markedly reduced the incidence of white blood cell (WBC) reduction (RR = 0.846, 95%CI = 0.760-0.941, P < 0.01), platelet reduction (RR = 0.462, 95% CI = 0.330-0.649, P < 0.01), and hemoglobin reduction (RR = 0.462, 95% CI = 0.330-0.649, P < 0.01) and alleviated drug-induced liver injury (RR = 0.677, 95%CI = 0.463-0.990, P < 0.05). However, it did not offer a significant protective effect (RR = 0.725, 95%CI = 0.358-1.468, P < 0.05). The effect of the combined treatment on the occurrence of vomiting was considerable (RR = 0.889, 95%CI = 0.794-0.996, P < 0.05), and the combined treatment markedly increased the immunity of patients with lung cancer. Conclusion: The combined treatment of Shenmai injection plus chemotherapy enhanced the short-term efficacy of chemotherapy, improved the patient quality of life, alleviated the adverse effects of chemotherapeutics, and increased the patient immunity. These results should be confirmed by large-scale, high-quality RCTs.

14.
J Asian Nat Prod Res ; 23(7): 627-636, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33985389

RESUMO

A phytochemical investigation on the 80% ethanol extract of the roots of Caragana stenophylla Pojark. resulted in the isolation of 20 compounds, including two new ones, named kompasinol P (2) and 3,5,7,2',3'-pentahydroxy-4'-methoxyisoflavanone (3). Among them, a pair of enantiomers, (7S, 8 R, 7'R, 8'S)-kompasinol A (1a) and (7 R, 8S, 7'S, 8'R)-kompasinol A (1b), were successfully separated by the chiral-phase HPLC resolution for the first time. The absolute configurations of 1a and 1b were determined by the experimental and calculated electronic circular dichroism (ECD) data. 15 isolates were evaluated for their anti-inflammatory activity via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Compounds 1a/1b, 6, 7, 9, 10, 12, 14, and 16-18 showed moderate inhibition with IC50 values ranging from 11.45 to 68.54 µM.


Assuntos
Caragana , Lignanas , Animais , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Camundongos , Estrutura Molecular
15.
Front Cell Dev Biol ; 9: 640476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869191

RESUMO

Plasmacytoid dendritic cells (pDC) are an essential immune microenvironment component. They have been reported for crucial roles in linking the adaptive and immune systems. However, the prognostic role of the pDC in breast cancer (BRCA) was controversial. In this work, we collected large sample cohorts and did a comprehensive investigation to reveal the relationship between pDC and BRCA by multiomics data analysis. Elevated pDC levels were correlated with prolonged survival outcomes in BRCA patients. The distinct mutation landscape and lower burden of somatic copy number alterations (SCNA) and lower intratumoral heterogeneity were observed in the high pDC abundance group. Additionally, a more sensitive immune response and chemotherapies response were observed in the high pDC group, which implicates that patients with high pDC abundance can be benefited from the combination of chemotherapy and immunotherapy. In conclusion, the correlation between pDC abundance and BRCA patients' overall survival (OS) was found to be positive. We identified the molecular profiles of BRCA patients with pDC abundance. Our findings may be beneficial in aiding in the development of immunotherapy and elucidating on the precision treatment for BRCA.

16.
Front Microbiol ; 12: 657887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868215

RESUMO

The members of the family Iridoviridae are large, double-stranded DNA viruses that infect various hosts, including both vertebrates and invertebrates. Although great progress has been made in genomic and phylogenetic analyses, the adequacy of the existing criteria for classification within the Iridoviridae family remains unknown. In this study, we redetermined 23 Iridoviridae core genes by re-annotation, core-pan analysis and local BLASTN search. The phylogenetic tree based on the 23 re-annotated core genes (Maximum Likelihood, ML-Tree) and amino acid sequences (composition vector, CV-Tree) were found to be consistent with previous reports. Furthermore, the information provided by synteny analysis and codon usage preference (relative synonymous codon usage, correspondence analysis, ENC-plot and Neutrality plot) also supports the phylogenetic relationship. Collectively, our results will be conducive to understanding the genera demarcation within the Iridoviridae family based on genomic synteny and component (codon usage preference) and contribute to the existing taxonomy methods for the Iridoviridae family.

17.
Plant Dis ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834854

RESUMO

Bacterial soft rot is an important disease of Chinese cabbage (Brassica rapa L. ssp. pekinensis) in China and many other countries. Four pectinolytic bacterial strains (WBC1, WBC6, WBC9 and WBC11) were isolated from soft-rotted Chinese cabbage in Beijing, China. Based on 16S rDNA and pmrA gene sequence analyses, multi-locus sequence analysis (MLSA), and genomic average nucleotide identity (ANI) analysis, these four strains were identified as Pectobacterium polaris. This species, previously reported from potato in countries not including China, is a new soft-rot pathogen of Chinese cabbage in China. Biochemical characteristics of these P. polaris strains tested by Biolog were mostly consistent with those of P. polaris NIBIO1006T. Their pathogenicity on Chinese cabbage is temperature-dependent, with all four strains as well as the type strain exhibiting high pathogenicity at 23°C and 28°C. These four strains infected Lactuca sativa, Daucus carota, Solanum tuberosum and Capsicum annuum by artificial inoculation. Specific PCR/qPCR primers for P. polaris were developed based on its specific gene sequences (determined using genome comparison methods). Both PCR and qPCR detected not only genomic DNA of P. polaris but also the pathogen from diseased plant tissues even before external symptoms appeared. Their detection sensitivities were as low as 1 pg and 100 pg genomic DNA of P. polaris, respectively. This study is the first to both report the emergence of P. polaris on Chinese cabbage in China, and provide rapid and accurate PCR/qPCR-based detection systems specific for P. polaris for the first time.

18.
J Endocrinol ; 249(3): 209-222, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-33847279

RESUMO

Currently, there are no conventional treatments for stress-induced cardiomyopathy (SCM, also known as Takotsubo syndrome), and the existing therapies are not effective. The recently discovered G protein-coupled estrogen receptor (GPER) executes the rapid effects of estrogen (E2). In this study, we investigated the effects and mechanism of GPER on epinephrine (Epi)-induced cardiac stress. SCM was developed with a high dose of Epi in adult rats and human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs). (1) GPER activation with agonist G1/E2 prevented an increase in left ventricular internal diameter at end-systole, the decrease both in ejection fraction and cardiomyocyte shortening amplitude elicited by Epi. (2) G1/E2 mitigated heart injury induced by Epi, as revealed by reduced plasma brain natriuretic peptide and lactate dehydrogenase release into culture supernatant. (3) G1/E2 prevented the raised phosphorylation and internalization of ß2-adrenergic receptors (ß2AR). (4) Blocking Gαi abolished the cardiomyocyte contractile inhibition by Epi. G1/E2 downregulated Gαi activity of cardiomyocytes and further upregulated cAMP concentration in culture supernatant treated with Epi. (5) G1/E2 rescued decreased Ca2+ amplitude and Ca2+ channel current (ICa-L) in rat cardiomyocytes. Notably, the above effects of E2 were blocked by the GPER antagonist, G15. In hiPSC-CM (which expressed GPER, ß1AR and ß2ARs), knockdown of GPER by siRNA abolished E2 effects on increasing ICa-L and action potential duration in the stress state. In conclusion, GPER played a protective role against SCM. Mechanistically, this effect was mediated by balancing the coupling of ß2AR to the Gαs and Gαi signaling pathways.


Assuntos
Epinefrina/farmacologia , Estradiol/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Estresse Fisiológico/efeitos dos fármacos
19.
Carbohydr Polym ; 259: 117756, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33674010

RESUMO

In order to find a facile and practical method to synthesize amino cellulose in bulk with high regional selectivity and high degree of substitution, the reaction conditions to brominate cellulose and to reduce azido group were carefully studied and some interesting phenomena were observed. With the optimized method, 6-amino-6-deoxy cellulose could be easily prepared with very simple separation techniques. The degree of substitution of the amino group amounted to 0.97 which was determined by 1H NMR spectrum of 6-benzamido-6-deoxy cellulose. Moreover, the amino group was evidenced to be at the C6 of glucose unit by 1H-1H COSY NMR and 1H-13C HSQC NMR spectra. In addition, three cellulose 6-acetamido-6-deoxy-2,3-bis(phenylcarbamate)s were prepared from the 6-amino-6-deoxy cellulose prepared with the techniques optimized in the present study. The developed cellulose derivatives were used as chiral selectors with which chiral stationary phases (CSPs) were prepared. The CSPs exhibited enantioseparation power to some chiral compounds.

20.
Int J Nanomedicine ; 16: 1525-1551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658782

RESUMO

Nanomedicines afford unique advantages in therapeutic intervention against tumors. However, conventional nanomedicines have failed to achieve the desired effect against cancers because of the presence of complicated physiological fluids and the tumor microenvironment. Stimuli-responsive drug-delivery systems have emerged as potential tools for advanced treatment of cancers. Versatile nano-carriers co-triggered by multiple stimuli in different levels of organisms (eg, extracorporeal, tumor tissue, cell, subcellular organelles) have aroused widespread interest because they can overcome sequential physiological and pathological barriers to deliver diverse therapeutic "payloads" to the desired targets. Furthermore, multiple stimuli-responsive drug-delivery systems (MSR-DDSs) offer a good platform for co-delivery of agents and reversing multidrug resistance. This review affords a comprehensive overview on the "landscape" of MSR-DDSs against tumors, highlights the design strategies of MSR-DDSs in recent years, discusses the putative advantage of oncotherapy or the obstacles that so far have hindered the clinical translation of MSR-DDSs.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Humanos , Imunoterapia , Nanomedicina Teranóstica , Microambiente Tumoral
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